Small membrane proteins regulate respiration in mitochondria

Energy conversion in living organisms is carried out by large protein complexes composed of multiple components. Small regulatory proteins control this process by changing the distance between these components and modulating their activities. In a recent publication, the structure of such a small regulatory protein was determined, revealing surprising features that are tightly linked to its function.

Respiration; the process by which food is degraded and combusted by the oxygen we breathe is central to life. In most multicellular organisms, respiration takes place in mitochondria, the ‘power plant’ of the cell. Mitochondrial respiration is carried out by a chain of protein complexes. This process needs to be tightly regulated in order to meet the specific needs of the cell at any given point in time. One such regulatory component is the Respiratory supercomplex factor (Rcf) 1. In a recently published study by researchers at the Department of Biochemistry and Biophysics, SU, the structure of this component was determined. Further, the work suggests that regulation is achieved by opening and closing of a “zipper”, composed of negative and positive charges, between two copies of the Rcf1 protein. This mechanisms could be a general regulatory principle in the living cell.

The Rcf1 protein was believed to be composed of one part that resides in the membrane and one part that forms large domain in water, outside the membrane. Our study showed that this picture is only partly correct since the Rcf1 proteins can bind to each other forming a ‘zipper’ interface which leads to the almost the entire molecule being found in the membrane. We suggest that the protein can switch between these two conformations and that interacts very differently with the respiratory chain complexes depending on its specific conformation, and that this dynamics is a key step in regulation.

Distribution of types of amino acids in the Rcf1 dimer structure and showing the putative membrane interface (dashed lines). (A) Stick representation and (B) Sphere representation of Rcf1 with hydrophobic side chains shown in yellow, polar side chains in gray, positively charged and negatively charged side chains are shown in blue and red, respectively.

The study on the Rcf1 protein is published in Proc. Natl. Acad. Sci. USA :